Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Chalcone Derivatives Containing Aminoguanidine Units

Chalcones are precursors of flavonoids or isoflavonoids, and they are abundant in edible plants. Chalcones constitute an important group of natural and synthetic products with a wide range of pharmacological activities.

To determine the seeds of the anti-tumor agents, we focused on the potential bioactive materials obtained from chalcone derivatives.

Two series of chalcone derivatives containing aminoguanidine or bis-chalone were designed, synthesized, and screened for their cytotoxicity, proliferation inhibition, and apoptosis-promoting activity in vitro against a panel of human tumor cell lines.

Among the various compounds studied in this work, 2-((E)-4-((E)-3-oxo-3-(p-tolyl)prop-1-en-1- yl)benzylidene)hydrazine-1-carboximidamide (5f) was the most potent, with IC50 values of 7.17 μM and 3.05 μM antiproliferative activity in vitro against human hepatocarcinoma HepG2 cells and SMMC-7721 cells, respectively. This result showed that the compound possessed a certain degree of selectivity for human hepatocarcinoma cells, especially for SMMC-7721. Then, Annexin V/PI flow cytometry assay was used to investigate different concentrations of compound 5f to demonstrate the ability of compound 5f in inducing apoptosis of SMMC-7721 cells in a concentrationdependent manner. Finally, these results were further verified by Western blot analysis.

Based on the collective results, compound 5f may be a promising anti-cancer compound, and may play a significant role in subsequent research.